Association between the insufficient improvement of the quantitative flow ratio and worsening outcomes in ST-segment elevated myocardial infarction: a multicentre prospective cohort study.

Background: Improved coronary physiological function after percutaneous coronary intervention (PCI) has been shown to improve prognosis in stable ischaemic heart disease, but has not yet been explored in ST-segment elevated myocardial infarction (STEMI). The study sought to determine whether an improvement in the quantitative flow ratio (QFR) could improve the prognosis of STEMI patients undergoing primary PCI. Methods: Patients diagnosed with STEMI who were receiving primary PCI were recruited for the study. Those with thrombolysis in myocardial infarction (TIMI) flow <2 after wiring were excluded. The ΔQFR was calculated using the following formula: ΔQFR = post-PCI QFR - pre-stent QFR. The primary endpoint was the composite event, including recurrent myocardial infarction (MI) and acute heart failure (AHF). Results: In total, 515 STEMI patients with a median follow-up of 364 days were enrolled in the study. Based on the cut-off value from the receiver operator characteristic (ROC) curve, the patients were divided into the following two groups: the lower ΔQFR group (≤0.25, N=332); and the normal ΔQFR group (>0.25, N=183). Patients with a lower ΔQFR had a relatively higher rate of MI/AHF (10.5% vs. 4.4%, P=0.019) and AHF (7.2% vs. 2.7%, P=0.044). A lower ΔQFR was significantly associated with a higher incidence of MI/AHF [hazard ratio (HR) =2.962, 95% confidence interval (CI): 1.358-6.459, P=0.006, respectively] after adjusting for potential confounders. Pre-stent angiographic microvascular resistance [odds ratio (OR) =1.027, 95% CI: 1.022-1.033, P<0.001] and the stent-to-vessel diameter ratio <1.13 (OR =1.766, 95% CI: 1.027-3.071, P=0.04) were independent predictors of a lower ΔQFR. Conclusions: An insufficient improvement in the QFR contributes to worsening outcomes and might be a useful tool for risk stratification in STEMI.

Long-term exposure to air pollutants and new-onset migraine: A large prospective cohort study.

BACKGROUNDS: Short-term exposure to air pollutants increases the risk of migraine, but the long-term impacts of exposure to multiple pollutants on migraine have not been established. The aim of this large prospective cohort study was to explore these links. METHODS: A total of 458,664 participants who were free of migraine at baseline from the UK Biobank were studied. Cox proportional hazards models were used to estimate the risk of new-onset migraine from combined long-term exposure to four pollutants, quantified as an air pollution score using principal component analysis. RESULTS: During a median (IQR) follow-up of 12.5 (11.8, 13.2) years, a total of 5417 new-onset migraine cases were documented. Long-term exposure to multiple air pollutants was associated with an increased risk of new-onset migraine, as indicated by an increased in the SDs of PM2.5 (hazard ratio (HR): 1.04, 95% CI: 1.01-1.06, P = 0.009), PM10 (HR: 1.07, 95% CI: 1.04-1.10, P < 0.001), NO2 (HR: 1.10, 95% CI: 1.07-1.13, P < 0.001) and NOx (HR: 1.04, 95% CI: 1.01-1.07, P = 0.005) in the main model. The air pollution score showed a doseresponse association with an increased risk of new-onset migraine. Similarly, compared with those of the lowest tertile, the HRs (95% CI) of new-onset migraine were 1.11 (95% CI: 1.04-1.19, P = 0.002) and 1.17 (95% CI: 1.09-1.26, P < 0.001) in tertiles 2 and 3, respectively, according to the main model (P trend < 0.001). CONCLUSION: Long-term individual and joint exposure to multiple air pollutants is associated with an increased risk of new-onset migraine.

Determinants and Prognoses of Visual-Functional Mismatches After Mechanical Reperfusion in ST-Elevation Myocardial Infarction.

Background: Discordance between the anatomy and physiology of the coronary has important implications for managing patients with stable coronary disease, but its significance in ST-elevation myocardial infarction has not been fully elucidated. Methods: The retrospective study involved patients diagnosed with ST-elevation myocardial infarction (STEMI) who underwent percutaneous coronary intervention (PCI), along with quantitative coronary angiography (QCA) and quantitative flow ratio (QFR) assessments. Patients were stratified into four groups regarding the severity of the culprit vessel, both visually and functionally: concordantly negative (QCA-diameter stenosis [DS] ≤ 50% and QFR > 0.80), mismatch (QCA-DS > 50% and QFR > 0.80), reverse mismatch (QCA-DS ≤ 50% and QFR ≤ 0.80), and concordantly positive (QCA-DS > 50% and QFR ≤ 0.80). Multivariable logistic regression analyses were conducted to identify the clinical factors linked to visual-functional mismatches. Kaplan‒Meier analysis was conducted to estimate the 18-month adverse cardiovascular events (MACE)-free survival between the four groups. Results: The study involved 310 patients, with 68 presenting visual-functional mismatch, and 51 exhibiting reverse mismatch. The mismatch was associated with higher angiography-derived microcirculatory resistance (AMR) (adjusted odds ratio [aOR]=1.016, 95% CI: 1.010-1.022, P<0.001). Reverse mismatch was associated with larger area stenosis (aOR=1.044, 95% CI: 1.004-1.086, P=0.032), lower coronary flow velocity (aOR=0.690, 95% CI: 0.567-0.970, P<0.001) and lower AMR (aOR=0.947, 95% CI: 0.924-0.970, P<0.001). Additionally, the mismatch group showed the worst 18-month MACE-free survival among the four groups (Log rank test p = 0.013). Conclusion: AMR plays a significant role in the occurrence of visual-functional mismatches between QCA-DS and QFR, and the mismatch group showed the worst prognosis.

The role of lifestyle in the association between long-term ambient air pollution exposure and cardiovascular disease: a national cohort study in China.

BACKGROUND: Cardiovascular disease (CVD) caused by air pollution poses a considerable burden on public health. We aim to examine whether lifestyle factors mediate the associations of air pollutant exposure with the risk of CVD and the extent of the interaction between lifestyles and air pollutant exposure regarding CVD outcomes. METHODS: We included 7000 participants in 2011-2012 and followed up until 2018. The lifestyle evaluation consists of six factors as proxies, including blood pressure, blood glucose, blood lipids, body mass index, tobacco exposure, and physical activity, and the participants were categorized into three lifestyle groups according to the number of ideal factors (unfavorable, 0-1; intermediate, 2-4; and favorable, 5-6). Satellite-based spatiotemporal models were used to estimate exposure to ambient air pollutants (including particles with diameters ≤ 1.0 µm [PM1], ≤ 2.5 µm [PM2.5], ≤ 10 µm [PM10], nitrogen dioxide [NO2], and ozone [O3]). Cox regression models were used to examine the associations between air pollutant exposure, lifestyles and the risk of CVD. The mediation and modification effects of lifestyle categories on the association between air pollutant exposure and CVD were analyzed. RESULTS: After adjusting for covariates, per 10 µg/m3 increase in exposure to PM1 (HR: 1.09, 95% CI: 1.05-1.14), PM2.5 (HR: 1.04, 95% CI: 1.00-1.08), PM10 (HR: 1.05, 95% CI: 1.03-1.08), and NO2 (HR: 1.11, 95% CI: 1.05-1.18) was associated with an increased risk of CVD. Adherence to a healthy lifestyle was associated with a reduced risk of CVD compared to an unfavorable lifestyle (HR: 0.65, 95% CI: 0.56-0.76 for intermediate lifestyle and HR: 0.41, 95% CI: 0.32-0.53 for favorable lifestyle). Lifestyle played a significant partial mediating role in the contribution of air pollutant exposure to CVD, with the mediation proportion ranging from 7.4% for PM10 to 14.3% for PM2.5. Compared to an unfavorable lifestyle, the relative excess risk due to interaction for a healthier lifestyle to reduce the effect on CVD risk was - 0.98 (- 1.52 to - 0.44) for PM1, - 0.60 (- 1.05 to - 0.14) for PM2.5, - 1.84 (- 2.59 to - 1.09) for PM10, - 1.44 (- 2.10 to - 0.79) for NO2, and - 0.60 (- 1.08, - 0.12) for O3. CONCLUSIONS: Lifestyle partially mediated the association of air pollution with CVD, and adherence to a healthy lifestyle could protect middle-aged and elderly people from the adverse effects of air pollution regarding CVD.

Remnant cholesterol, iron status and diabetes mellitus: a dose-response relationship and mediation analysis.

BACKGROUND: Remnant cholesterol (RC) is recognized as a risk factor for diabetes mellitus (DM). Although iron status has been shown to be associated with cholesterol metabolism and DM, the association between RC, iron status, and DM remains unclear. We examined the relationship between RC and iron status and investigated the role of iron status in the association between RC and DM. METHODS: A total of 7308 patients were enrolled from the China Health and Nutrition Survey. RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Iron status was assessed as serum ferritin (SF) and total body iron (TBI). DM was ascertained by self-reported physician diagnosis and/or antidiabetic drug use and/or fasting plasma glucose ≥ 126 mg/dL and/or glycated haemoglobin ≥ 6.5%. General linear models were used to evaluate the relationships between RC and iron status. Restricted cubic splines were used to assess the association between RC and DM. Mediation analysis was used to clarified the mediating role of iron status in the association between the RC and DM. RESULTS: The average age of the participants was 50.6 (standard deviation = 15.1) years. Higher RC was significantly associated with increased SF (ß = 73.14, SE = 3.75, 95% confidence interval [CI] 65.79-80.49) and TBI (ß = 1.61, SE = 0.08, 95% CI 1.44-1.78). J-shape relationships were found in the association between RC levels with DM, as well as iron status with DM. Significant indirect effects of SF and TBI in the association between RC and DM were found, with the index mediated at 9.58% and 6.37%, respectively. CONCLUSIONS: RC has a dose-response relationship with iron status. The association between RC and DM was mediated in part by iron status. Future studies are needed to confirm these findings and further clarify the underlying mechanism.

Transition of visceral adiposity index and risk of cardiovascular disease in middle-aged and older Chinese adults.

OBJECTIVE: Visceral obesity and the lifetime risk of cardiovascular disease (CVD) have received increasing attention. However, the relationship between dynamic changes in visceral obesity and CVD has not been studied. We aimed to determine the association of visceral adiposity index (VAI) transition with CVD risk. METHODS: A total of 5395 participants were recruited in 2011-2012 and followed up until 2018 from the China Health and Retirement Longitudinal Study. The cut-off value of the VAI was obtained by the receiver-operating characteristic curve. Participants were grouped based on VAI change patterns during the follow-up period (2011-2015): the low-low group, low-high group, high-low group, and high-high group. CVD was defined as a medical diagnosis of heart disease and/or stroke. A Cox proportional hazards model was used to evaluate the correlation between VAI transition and CVD. RESULTS: Over a median follow-up period of 7 years, 969 participants (17.9 %) developed CVD. VAI change patterns were significantly associated with CVD risk after adjustment for demographic characteristics and risk factors. The high-high group (hazard ratio (HR): 1.65, 95 % confidence interval (CI): 1.39-1.97) and the low-high group (HR: 1.29, 95 % CI: 1.04-1.61) were associated with a higher risk of CVD after adjusting for demographic characteristics and traditional risk factors compared to the low-low group, while the effect in the high-low group was not significant. CONCLUSIONS: VAI transition was significantly associated with the risk of CVD. Monitoring the dynamics of the VAI in public health practice would help prevent CVD.

Outdoor artificial light at night and incident cardiovascular disease in adults: A national cohort study across China.

Cardiovascular diseases (CVDs) become a major public health concern. Evidence concerning the effects of outdoor artificial light at night (ALAN) on CVD in adults is scarce. We aimed to investigate the extent to which outdoor ALAN could affect the risk of CVD over a exposure range. Data from the China Health and Retirement Longitudinal Study, a population-based longitudinal study, launched in 2011-2012 and follow up till 2018, covering 28 provinces, autonomous regions and municipalities across mainland China. This study included 14,097 adults aged ≥45 years. Outdoor ALAN exposure (in nanowatts per centimeters squared per steradian) within 500 m of each participant's baseline residence was obtained from satellite image data. CVD was defined from medical diagnosis. The population was divided into three groups based on outdoor ALAN exposure from low to high. Cox regression model was used to estimate the association between outdoor ALAN exposure and incident CVD with hazard ratios (HRs) and 95 % confidence intervals (CIs). The mean (SD) age of the cohort was 57.6 (9.1) years old and 49.3 % were males. Outdoor ALAN exposure of study participants ranged from 0.02 to 39.79 nW/cm2/sr. During 83,033 person-years of follow-up, 2190 (15.5 %) cases of CVD were identified. Both low (HR: 1.21; 95 % CI: 1.02-1.43) and high (HR: 1.23; 95 % CI: 1.04-1.46) levels of outdoor ALAN exposure group were associated with higher risk of CVD compared with intermediate levels of outdoor ALAN exposure group. Body mass index was a significant effect modifier in the association between outdoor ALAN and risk of CVD, with stronger effects among those who was overweight or obese. The findings of this study suggest that low and high outdoor ALAN exposure were associated with a higher risk for CVD. More attention should be given to the cardiovascular effects associated with outdoor ALAN exposure.

Association between outdoor light at night and hypertension and high-normal blood pressure: A nationwide cross-sectional study among Chinese adults.

The authors aimed to investigate the association between outdoor light at night (LAN) intensity and blood pressure. The study included 13 507 participants aged 45 and above from the 2011-2012 China Health and Retirement Longitudinal Study baseline survey. Blood pressure measurements were obtained by averaging the last two readings recorded (three measurements with an interval of 45-60 s between each measurement) during the survey. Outdoor LAN intensity was assessed using Defense Meteorological Satellite Program data. The study categorized participants based on quartiles of outdoor LAN intensity and employed statistical methods like linear regression, restricted cubic splines, and logistic models to analyze the connections. After adjusting for potential confounding factors, higher levels of outdoor LAN intensity were associated with increase in systolic blood pressure (0.592 mmHg/interquartile range [IQR], 95% confidence interval [CI]: 0.027,1.157), diastolic blood pressure (0.853 mmHg/IQR, 95% CI: 0.525,1.180) and mean arterial pressure (0.766 mmHg/IQR, 95% CI: 0.385,1.147). Interestingly, the relationship between LAN intensity and odds of hypertension followed a non-linear pattern, resembling a reverse "L" shape on cubic splines. Participants with the highest quartile of outdoor LAN intensity had 1.31-fold increased odds of hypertension (95% CI: 1.08-1.58) compared to the lowest quartile. Additionally, there was an observable trend of rising odds for high-normal blood pressure with higher levels of LAN intensity in the crude model, but no statistically significant differences were observed after adjusting for confounding factors. In conclusion, this study underscores a significant connection between outdoor LAN intensity and the prevalence of hypertension.

Inflammatory Risk Status Shapes the Association Between Uric Acid and Cognitive Function in Non-Hyperuricemia Middle Aged and Elderly.

BACKGROUND: The association between uric acid (UA) and cognitive function still remains controversial. Moreover, the role of inflammation in the above association is also unclear. OBJECTIVE: We aimed to determine the association between UA and cognitive function among non-hyperuricemia adults, and in particular, whether the association was shaped by different inflammation levels. METHODS: From the China Health and Retirement Longitudinal Study (CHARLS), 7,272 participants aged 45 and above were enrolled in 2011. Cognitive function measurement included orientation and attention, episodic memory, and visuospatial ability. Fasting blood samples were collected to measure levels of UA and high-sensitivity C-reactive protein (hs-CRP). Generalized estimating equation models were used to evaluate the effect of UA on cognitive function in all participants and those at different levels of hs-CRP (hs-CRP <3 mg/L or ≥3 mg/L). RESULTS: Among non-hyperuricemia adults (mean age: 58.08, 49.59% males) for a median of 7 years follow-up, participants with higher levels of UA had better cognitive function score compared to those with lower UA levels (ß: 0.09, 95% confidence interval [CI]: 0.01-0.17, p = 0.023). And this association was significant under low-grade inflammation levels condition (ß:0.10, 95% CI: 0.10-0.19, p = 0.024), but not in high-grade inflammation levels condition. Further, the cognitive function benefit of elevated UA existed only in people with persistent low-grade inflammation levels at a longitudinal perspective (ß: 0.14, 95% CI: 0.01-0.27, p = 0.039). CONCLUSIONS: Elevated UA levels were associated with better cognitive function in non-hyperuricemia population, especially for those at low inflammation levels.

Association between remnant cholesterol, metabolic syndrome, and cardiovascular disease: post hoc analysis of a prospective national cohort study.

BACKGROUND: Epidemiologic evidence suggested that remnant cholesterol (RC) is associated with the occurrence of cardiovascular disease (CVD). In recent years, RC has been connected with different types of cardiometabolic disorders. We aim to clarify the relationship among RC, metabolic syndrome (MetS) and subsequent CVD. METHODS: We enrolled 7471 individuals into our study from China Health and Nutrition Survey in 2009 and followed participants till 2015. RC was calculated as total cholesterol minus low-density lipoprotein cholesterol minus high-density lipoprotein cholesterol. CVD was defined as myocardial infarction and stroke. Multivariate logistic regression and Cox regression models were used to evaluate the association between RC and MetS as well as CVD. We further investigated whether the association between RC and CVD was mediated by MetS. RESULTS: Of all subjects, 24.73% were diagnosed with MetS and 2.74% developed CVD. Multivariate logistic regression analysis elucidated that per-tertile-increase in RC was associated with MetS after adjusting all the confounder factors, (odds ratio: 3.49, 95% confidence interval CI 3.21-3.79, P for trend < 0.001). And per-tertile-increase RC had a significant increased risk of CVD (hazard ratio: 1.26, 95% CI 1.06-1.50, P for trend = 0.008). Meanwhile, we found that RC level is associated with the prevalence of all the components of MetS. Significant indirect effects of RC between MetS and CVD were found, with the index mediated at 48.46% of the association. CONCLUSIONS: Our study provides the evidence that RC level is independently associated with the prevalence of MetS and each component of MetS. MetS partially mediated the association between RC level and CVD risk.

Lipoprotein(a) as a Higher Residual Risk for Coronary Artery Disease in Patients with Type 2 Diabetes Mellitus than without.

Purpose: Lipoprotein(a) (Lp[a]) is well-known as a residual risk factor for coronary artery disease (CAD). However, the different adverse effects of Lp(a) about CAD in patients with or without type 2 diabetes mellitus (T2DM) are unclear. This study aimed to investigate the Lp(a) thresholds for CAD diagnosis in T2DM and non-T2DM patients, and further compare the Lp(a) alarm values along with optimal low-density lipoprotein cholesterol (LDL-C) level. Methods: This retrospective study consecutively enrolled patients with suspected CAD who underwent coronary angiography in Guangdong Provincial People's Hospital between September 2014 and July 2015. A logistic regression model was established to explore the association of Lp(a) and CAD in patients. Restricted cubic splines were used to compare the threshold values of Lp(a) for CAD in patients with and without T2DM, and further in optimal LDL-C level situation. Results: There were 1522 patients enrolled finally. After multivariable adjustment, Lp(a) was an independent risk factor for CAD in patients with T2DM (odds ratio [OR]: 1.98, 95% CI]: 1.12-3.49, p = 0.019) and without T2DM (OR: 3.42, 95% CI: 2.36-4.95, p < 0.001). In the whole population, the Lp(a) threshold of CAD was 155, while 145 mg/L for T2DM and 162 mg/L for non-T2DM ones, respectively. In patients with LDL-C<1.8 mmol/l, the alarm value of Lp(a) was even lower in T2DM than non-T2DM patients (155 vs 174 mg/L). Conclusion: Lp(a) was a significant residual risk for CAD in patients whether with T2DM or not. And Lp(a) had a lower alarm value in T2DM patients, especially in optimal LDL-C level.

Effects of atorvastatin and rosuvastatin on dysfunctional coronary circulation in patients with ST-segment elevation myocardial infarction.

OBJECTIVE: Evidence of therapy for dysfunctional coronary circulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) is limited. This study was performed to compare the effects of atorvastatin and rosuvastatin on dysfunctional coronary circulation. METHODS: This retrospective study enrolled 597 consecutive patients with STEMI who underwent pPCI in 3 centers from June 2016 to December 2019. Dysfunctional coronary circulation was defined by the thrombolysis in myocardial infarction (TIMI) grade and the TIMI myocardial perfusion grade (TMPG). Logistic regression analysis was used to evaluate the impact of different statin types on dysfunctional coronary circulation. RESULTS: The incidence of TIMI no/slow reflow did not differ between the two groups, but the incidence of TMPG no/slow reflow was significantly lower in the atorvastatin than rosuvastatin group (44.58% vs. 57.69%, respectively). After multivariate adjustment, the odds ratio with 95% confidence interval of rosuvastatin was 1.72 (1.17-2.52) for after pretreatment TMPG no/slow reflow and 1.73 (1.16-2.58) for after stenting TMPG no/slow reflow. Atorvastatin and rosuvastatin showed no significant differences in clinical outcomes during hospitalization. CONCLUSIONS: Compared with rosuvastatin, atorvastatin was associated with better coronary microcirculatory perfusion in patients with STEMI who underwent pPCI.

Long-term exposure to ambient air pollution, circadian syndrome and cardiovascular disease: A nationwide study in China.

OBJECTIVES: Epidemiological evidence suggests associations between ambient air pollution and cardiovascular disease (CVD), while circadian rhythm dysregulation, presented by circadian syndrome (CircS), is emerging as a new proxy to cardiovascular disorder that could provide a bridge between them. The present study aims to clarify the effect of high levels ambient air pollution exposure on CircS and CVD in China. METHODS: From the China Health and Retirement Longitudinal Study, we recruited 9116 Chinese participants in 2011 and followed them to 2015. A spatiotemporal model was applied to estimate exposure to particles with diameters ≤2.5 µm (PM2.5). The variable CircS was defined based on 7 components, including the 5 components used to define metabolic syndrome as well as other two components, lack of sleep and depression. The associations between PM2.5 exposure and prevalent CircS as well as incident CVD were modeled via logistic regression analysis displaying odds ratios (ORs) and 95 % CIs (confidence intervals). A mediation analysis was undertaken to identify the potential mediating role of CircS between PM2.5 exposure and CVD. RESULTS: The mean age (standard deviation) was 59 (9) and 48.22 % were male. The OR (95 % CI) between the highest (Q4) and the lowest (Q1) quartile of PM2.5 exposure for CircS was 1.13 (1.01-1.28) in 2011 and 1.44 (1.22-1.72) in 2015. The cumulative effect of the components of CircS became more obvious with the increase of the PM2.5 quartile exposure. For the Q4 versus Q1 of PM2.5 increment, the multivariate-adjusted OR (95 % CI) was 1.66 (1.20-2.29) for CVD incidence. CircS partially mediated the association between PM2.5 exposure and CVD. CONCLUSIONS: Exposure to PM2.5 is a risk factor for CircS and CVD, and the effect of PM2.5 on CVD may be explained by CircS. Improving air quality would have high value in preventing CircS as well as CVD in public health.

Fatal coronary artery spasm triggered before transseptal puncture for mitral transcatheter edge-to-edge-repair: a case report.

Background: Transient ST-segment elevation or coronary artery spasm during transseptal catheterization has been previously described. Most cases were either reversible or asymptomatic. Case summary: We present a case of severe multiple coronary artery spasms with advanced atrioventricular block and ventricular fibrillation during compression of the fossa ovalis by a sheath catheter, before the performance of the transseptal puncture procedure for mitral transcatheter edge-to-edge-repair. Discussion: The mechanical effects of forward tension from transseptal puncture on the interatrial vagal network could be the most possible explanation for the occurrence of this phenomenon.

Novel hybrid virtual screening protocol based on pharmacophore and molecular docking for discovery of GSK-3ß inhibitors.

GSK-3ß is a member of the GSKs subfamily and plays a major role in the regulation of transcriptional elongation, which has attracted widespread attention as a therapeutic target for AD. In this study, by combining pharmacophore-based virtual screening and kinase inhibition assays, we have successfully identified four small molecules that inhibit GSK-3ß activity at micromolar potency. These hit compounds showed drug-like properties according to Lipinski's rule of five and ADMET. An inter-complex interaction study showed that all hit compounds adapted well to the ATP pocket of the GSK-3ß protein. Among them, hits 2 and 4 displayed considerable inhibitory activities with IC50 value of 0.74 ± 0.04 µM and 2.32 ± 0.84 µM respectively. Overall, the discovered GSK-3ß inhibitors act as new chemical leads to develop improved inhibitors that block the interaction of GSK-3ß, and the hybrid virtual screening strategy designed in this study provides an important reference for design and synthesis novel selective GSK-3ß inhibitors.

Chemokine signaling synchronizes angioblast proliferation and differentiation during pharyngeal arch artery vasculogenesis.

Developmentally, the great vessels of the heart originate from the pharyngeal arch arteries (PAAs). During PAA vasculogenesis, PAA precursors undergo sequential cell fate decisions that are accompanied by proliferative expansion. However, how these two processes are synchronized remains poorly understood. Here, we find that the zebrafish chemokine receptor Cxcr4a is expressed in PAA precursors, and genetic ablation of either cxcr4a or the ligand gene cxcl12b causes PAA stenosis. Cxcr4a is required for the activation of the downstream PI3K/AKT cascade, which promotes not only PAA angioblast proliferation, but also differentiation. AKT has a well-known role in accelerating cell-cycle progression through the activation of cyclin-dependent kinases. Despite this, we demonstrate that AKT phosphorylates Etv2 and Scl, the key regulators of angioblast commitment, on conserved serine residues, thereby protecting them from ubiquitin-mediated proteasomal degradation. Altogether, our study reveals a central role for chemokine signaling in PAA vasculogenesis through orchestrating angioblast proliferation and differentiation.

Long-term trajectories of BMI and cumulative incident metabolic syndrome: A cohort study.

Background: Body mass index (BMI) has been widely recognized as a risk factor for metabolic syndrome (MetS). However, the relationship between the trajectory of BMI and cumulative incident MetS is still unclear. We investigate the associations of long-term measurements of BMI with MetS among young adults in the China Health and Nutrition Survey. Methods: We enrolled individuals aged 10 to 20 at baseline with recorded BMI at each follow-up interview, and 554 participants were finally included in our study. The assessment and incidence of MetS were evaluated by blood tests and physical examinations in their adulthood. A latent class growth mixed model was used to identify three BMI trajectory patterns: a low baseline BMI with slow development (low-slow, n=438), a low baseline BMI with fast development (low-fast, n=66), and a high baseline BMI with fast development (high-fast, n=50). Logistic regression was used to explore the relationship between different BMI trajectories and the incidence of MetS. Result: During a follow-up of 16 years, 61 (11.01%) participants developed MetS. The combination of elevated triglycerides and reduced high-density lipoprotein cholesterol was most frequent in diagnosed MetS. In multivariate adjusted models, the low-fast and high-fast BMI trajectories showed a significantly higher risk of MetS than those with the low-slow BMI trajectory (low-high: OR = 3.40, 95% CI: 1.14-10.13, P < 0.05; high-fast: OR = 5.81, 95% CI: 1.63-20.69, P < 0.05). Conclusion: Our study identified three BMI trajectories in young adults and found that long-term measurements of BMI were also associated with cumulative incident MetS.

Triglyceride-glucose index is associated with quantitative flow ratio in patients with acute ST-elevation myocardial infarction after percutaneous coronary intervention.

Background: The triglyceride-glucose (TyG) index is a novel marker representing the degree of insulin resistance (IR) and is closely related to cardiovascular diseases. However, the association between the TyG index and vascular function in patients with acute ST-elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) remains unknown. Materials and methods: This study was a post hoc analysis of a multicenter, prospective cohort study. In this study, patients with STEMI who underwent PCI were included, and coronary angiography data were analyzed by Quantitative coronary angiography (QCA) and quantitative flow ratio (QFR). In addition, the TyG index was calculated as follows: Ln [fasting triglyceride (mg/dl) × fasting blood glucose (mg/dl) × 1/2]. According to the post-PCI QFR, patients were divided into two groups: post-PCI QFR ≤ 0.92 group and post-PCI QFR > 0.92 group. Construction of logistic regression model to explore the relationship between the TyG index and post-PCI QFR. Results: A total of 241 STEMI patients were included in this study. Compared with patients in the post-PCI QFR > 0.92 group, the TyG index was higher in the post-PCI QFR ≤ 0.92 group. Logistic regression model showed that after adjusting for other confounding factors, the TyG index was positively correlated with the risk of post-PCI QFR ≤ 0.92 (OR = 1.697, 95% CI 1.171-2.460, P = 0.005). Restricted cubic splines showed the cutoff value of TyG index associated with post-PCI QFR ≤ 0.92 risk was 9.75. Conclusion: The TyG index was associated with the risk of post-PCI QFR ≤ 0.92 in STEMI patients. The risk of post-PCI QFR ≤ 0.92 increased when the TyG index exceeded 9.75.

Air quality improvement and cognitive function benefit: Insight from clean air action in China.

INTRODUCTION: Epidemiological evidence suggests associations between long-term exposure to air pollution and accelerated cognitive decline. China implemented a strict clean air action plan in 2013; however, it is unclear whether the improvement of air quality has alleviated cognitive impairment in the population. METHODS: From the China Health and Retirement Longitudinal Study, 8536 Chinese adults were enrolled in 2011 and followed up in 2015. Satellite-based spatiotemporal models were used to estimate exposure to air pollutants (including particles with diameters ≤1.0 µm [PM1], ≤2.5 µm [PM2.5], ≤10 µm [PM10], nitrogen dioxide [NO2], and ozone [O3]). Cognitive function was evaluated using a structured questionnaire in three dimensions: episodic memory, orientation and attention, and visuoconstruction. The associations between changes in the levels of air pollutants and cognitive function were elucidated by a logistic model. The Bayesian Kernel Machine Regression (BKMR) model was applied to evaluate the cumulative effect of air pollutants. RESULTS: The mean (standard deviation) age of all participants was 58.6 (8.7) years. The odds ratio (95% confidence interval) between the highest and the lowest quartile of PM1 exposure reduction for cognitive impairment was 0.46 (0.41, 0.53) after adjusting for confounders. Similar protective effects of cognitive function were observed with the decrease in the level of PM2.5 (0.34 [0.30, 0.39]), PM10 (0.54 [0.48, 0.62]), and NO2 (0.59 [0.51, 0.67]), while the reduction in O3 appeared to be less related to changes in cognitive function (OR: 0.97 [0.85, 1.10]). The protective association of PM1 reduction was stronger in males than in females. Decreased in PM2.5 dominate the cognitive function benefit relative to PM1, PM10, NO2. CONCLUSIONS: The implementation of the clean air action plan led to a significant reduction in PM1, PM2.5, PM10, and NO2, which could slow the decline of cognitive function, while a reduction in O3 may not.

D-Dimer Is Associated With Coronary Microvascular Dysfunction in Patients With Non-obstructive Coronary Artery Disease and Preserved Ejection Fraction.

Background: Coronary microvascular dysfunction (CMVD), an important etiology of ischemic heart disease, has been widely studied. D-dimer is a simple indicator of microthrombosis and inflammation. However, whether an increase in D-dimer is related to CMVD is still unclear. Materials and Methods: This retrospective study consecutively enrolled patients with myocardial ischemia and excluded those with obstructive coronary artery. D-dimer was measured at admission and the TIMI myocardial perfusion grade (TMPG) was used to distinguish CMVD. Patients were divided into the two groups according to whether the D-dimer was elevated (>500 ng/ml). Logistic models and restricted cubic splines were used to explore the relationship between elevated D-dimer and CMVD. Results: A total of 377 patients were eventually enrolled in this study. Of these, 94 (24.9%) patients with CMVD had older age and higher D-dimer levels than those without CMVD. After full adjustment for other potential clinical risk factors, patients with high D-dimer levels (>500 ng/ml) had a 1.89-times (95% CI: 1.09-3.27) higher risk of CMVD than patients with low D-dimer levels. A non-linear relationship was found between concentrations of D-dimer and CMVD. With increased D-dimer level, the incidence of CMVD increased and then remained at a high level. Stratified analysis was performed and showed similar results. Conclusion: Elevated D-dimer level is associated with the incidence of CMVD and potentially serves as a simple biomarker to facilitate the diagnosis of CMVD for patients with angina.